Why does hormonal contraception and menopausal hormonal treatment have such a small effect on breast cancer risk?

Abstract

Oestrogen is considered by many to be a major cause of breast cancer, and yet hormonal contraception and menopausal hormonal therapy have a paradoxically small effect on breast cancer risk. Also, in the oestrogen-only arm of the Women's Health Initiative, subjects given oestrogen had a reduced risk of breast cancer compared to controls. Initiation of breast cancer likely begins early in life, in the long-lived ER−PR− breast stem cell. The main mitogen of ER+PR+ breast cancers is oestrogen derived from local breast fat and the tumour itself, rather than circulating oestrogens. Progesterone is relatively breast neutral, but progestins in the laboratory have been shown to expand malignant breast stem cell number.